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C─H⋯O hydrogen bonds constitute a unique class of cohesive interactions. Their properties are similar to those of canonical H‐bonds, although their energy is significantly lower, typically in the 0.5–2.5 kcal/mol range. Polarised C─H groups, such as those adjacent to electronegative groups, or within aromatic moieties, are particularly strong donors. C─H⋯O bonds are ubiquitous in nucleic acids and in proteins, notably stabilizing the β‐sheet secondary structure. They have also been observed in numerous protein‐ligand interactions. Here, we analysed crystal structures, deposited in the Protein Data Bank, of complexes of FDA‐approved protein kinase inhibitors with cognate kinases, to assess the possible role of C─Hinhibitor⋯Oprotein hydrogen bonds. The conserved hinge motif of protein kinases with two solvent‐exposed carbonyl groups and one exposed backbone amide, is well known to be involved in canonical H‐bonding with inhibitors. We now find that in virtually all complexes where the inhibitor interacts with the hinge backbone, at least one of the hinge carbonyl groups accepts an H‐bond from a C─H inhibitor group, which is either aromatic or adjacent to an electronegative group. These observations are important for design of hinge‐binding scaffolds of novel kinase inhibitors for therapeutic use. [ABSTRACT FROM AUTHOR]